Ethyl Acetate → HCID 57410977, compound

HRID 1502328Notes

Reaction equation

HRID 1502328 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[OH:18][CH2:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:18][CH2:19][C:20]1[CH:25]=[C:24]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]4[CH2:17][CH2:16]4)=[O:14])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)[CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 57410977HCID 57410977, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (100 mg, 0.35 mmol), 3-(hydroxyl-methyl)phenylboronic acid (0.53 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (26 mg, 0.035 mmol) and cesium carbonate (228 mg, 0.70 mmol) in 1,2-dimethoxyethane/water (10:1, 2.0 mL) was stirred under microwave irradiation at 130° C. for 20 minutes under nitrogen. Ethyl acetate (10 mL) was added to the reaction mixture and it was filtered. The residue was extracted with ethyl acetate (5.0 mL×3). The organic layer was combined, dried with sodium sulfate, filtered and concentrated. It was purified by column chromatography to give the product (10 mg, 13%). LCMS (ESI): RT (Min)=1.062, M+H+=318.2, method=A. 1H NMR (400 MHz, CDCl3) δ 10.91 (s, 1H), 9.18 (s, 1H), 8.44 (s, 1H), 8.30 (s, 1H), 8.01 (dd, J=1.6, 8.8 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.73 (s, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.46 (t, J=6.8 Hz, 1H), 7.34 (d, J=7.2 Hz, 1H), 5.29 (t, J=5.6 Hz, 1H), 4.58 (d, J=6.0 Hz, 2H), 2.07-2.04 (m, 1H), 0.83-0.79 (m, 4H).

Workup

  1. filtrationwas filtered
  2. extractionThe residue was extracted with ethyl acetate (5.0 mL×3)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customIt was purified by column chromatography

Sources & evidence

ORD record
ord-40df6955eeaf40c59b1a676bd13be11a
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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